Atraumatic Adjustment or Replacement of a Device for Treating Valve Regurgitation

ABSTRACT

An epicardial device for reducing or preventing regurgitation of blood through a valve of a heart includes a main body having a segment adapted to apply force to an epicardial surface of the heart. A member that applies counterforce to the force applied by the segment is also provided. A foundation is configured to be anchored to the epicardial surface of the heart. The foundation includes a surface configured with attachment features. The device further includes a surface configured with mating attachment features configured to attach to the attachment features of the foundation. The mating attachment features and attachment features are separable and reattachable to allow repositioning of at least a portion of the device relative to the foundation.

CROSS-REFERENCE

This application claims the benefit of U.S. Provisional Application Ser.Nos. 62/622,831, filed Jan. 27, 2018; 62/622,830, filed Jan. 27, 2018;and 62/622,827, filed Jan. 27, 2018, each of which applications ishereby incorporated herein, in its entirety, by reference thereto.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference. Thisspecification specifically incorporates US Patent ApplicationPublication Nos. 2010/0004504 A1 and 2012/0323314 A1 herein, in theirentireties, by reference thereto. Also specifically incorporated byreference in their entireties, are U.S. Provisional Application Ser.Nos. 62/622,831, 62/622,827; and 62/622,830, as noted above. Further,this specification specifically incorporates in its entiretyInternational Application Serial No. (PCT serial no. not yet assigned,Attorney's Docket No. MITR-005WO), titled “Epicardial Valve RepairSystem”, filed concurrently herewith; International Application SerialNo. (PCT serial no. not yet assigned, Attorney's Docket No.CHINE-001WO), titled “Self-Adjusting Device”, filed concurrentlyherewith; and U.S. Application Serial No. (US application serial no. notyet assigned, Attorney's Docket No. MITR-003), titled “ManuallyAdjustable Device”, filed concurrently herewith.

FIELD OF THE INVENTION

This invention applies to the field of cardiac surgery and morespecifically, to treatment of a heart valve.

BACKGROUND OF THE INVENTION

There is broad prevalence of various organ diseases directly related tomechanical compromise of the organ tissues and/or functions. Variousones of these conditions are degenerative and progressive, for exampledegenerative mitral valve regurgitation. Mitral Valve Regurgitation (MR)affects 2% of the population worldwide, but less than 20% of people indeveloped countries who are diagnosed each year with MR undergo acardiac surgery procedure. Left untreated, MR is a risk factor and canlead to heart failure. In addition, it is estimated that 20% of patientswith heart failure and 15% of post-myocardial infarction patients haveat least moderate MR.

The mitral valve is located between the left atrium and the leftventricle of the heart. During normal operation, the mitral valve opensduring diastole, allowing blood to flow from the left atrium into theleft ventricle. During systole, the mitral valve closes, causing highpressure blood to exit the left ventricle through the aorta. Mitralvalve regurgitation is a cardiac condition in which the posteriorleaflet of the mitral valve does not fully contact the anterior leafletof the valve during systole, thus a gap remains between the leaflets ofthe mitral valve during systole. The gap remaining between the leafletsallows retrograde blood flow to pass from the left ventricle into theleft atrium through the mitral valve. This is referred to as mitralregurgitation, or mitral valve regurgitation. Mitral regurgitationreduces the volume of blood pumped out of the heart to the aorta duringeach cardiac cycle, thus reducing the efficiency of the heart. Mitralregurgitation may exist for any of several reasons, including congenitalmalformations of the valve, ischemic disease, or effects ofcardiomyopathy, such as dilated (congestive) cardiomyopathy (i.e.,enlarging of the heart). Enlargement of the left ventricle of the heartwith a corresponding increase in the diameter of the mitral valveannulus prevents the two leaflets of the mitral valve from co-apting andprevents them from properly preventing blood flow from the leftventricle to the left atrium during contraction of the heart.

Conventional techniques for treating dysfunctions of the mitral valvetypically include highly invasive, open heart surgical procedures inorder to replace or repair the dysfunctioning mitral valve. Somesurgical procedures include the implantation of a replacement valve(e.g., animal valve or artificial mechanical valve). Other techniquesinclude the use of annuloplasty rings which are surgically placed aroundthe annulus of the mitral valve within the chamber of the heart andsutured into place. The presence of the annuloplasty ring alters thegeometry of the annulus of the mitral valve in order to improvecoaptation of the leaflets of the valve. Epicardial clips have also beenproposed and used to alter the geometry of the annulus of the mitralvalve. Another surgical technique which requires accessing one or morechambers of the heart is leaflet coaptation. Leaflet coaptation (e.g.,Alfieri edge-to-edge repair) is a surgical procedure in which the valveleaflets are sutured together (e.g., bow-tie suture) to improvecoaptation of the leaflets. A further surgical technique includesextending a tensioning cord across a chamber of the heart to alter thegeometry of the heart chamber. The tensioning cord, which extendsthrough a chamber of the heart, and thus is in contact with blood in theheart chamber, pulls opposing walls of the heart toward one another toreduce heart wall tension and/or reposition the papillary muscles withinthe chamber. These techniques typically require opening the heart and/orentering one or more of the chambers of the heart to gain direct accessto the mitral valve. Recent randomized trials in heart failure and theMitraClip device found that reducing mitral regurgitation arrested thedilation of the left ventricle, common in the heart failure cycle.Grayburn et al, “Proportionate and Disproportionate Functional MitralRegurgitation” JACC: Cardiovascular Imaging, 2018 cited that longevityand improved quality of life paralleled left ventricular volumereductions. It is reasonable that designs that reduce both mitralregurgitation and cardiac volume may have profound clinical benefits.

All of the aforementioned treatments are static approaches to treatmentof the disease. That is, the configurations of the devices used to treatthe disease remain fixed at the time of performing the procedure. Forexample, implantation of a device to treat mitral valve regurgitationresults in a fixed application of force and/or configuration of thedevice at the time that the device is implanted. If, after implantingsuch a device a configuration needs to be altered or force applicationneeds to be altered, this requires a removal of the device andre-implantation of the same device in an altered location orimplantation of another, differently sized device or reconfigureddevice. To avoid such occurrences requires a great deal of precisionwith regard to the configuration/force applied by an implant device atthe time of implantation. These requirements are exacerbated byprocedures performed while the heart is beating.

Therefore, it may be desirable to devise a less invasive technique fortreatment of diseases such as mitral valve regurgitation, wherein thetreatment applied may be adjusted after fixation of an implant, butbefore closing the patient to complete the implantation procedure.

It may be further desirable to provide devices that include componentsthat can be implanted under direct visualization by a surgeon, withcompletion of the implantation being performed when the surgeon can nolonger directly visualize the location where implantation is beingcompleted.

It may further be desirable to provide adjustable devices which maintaina desired configuration after adjustment, without concern for changingconfiguration after completion of the adjustment.

It may be desirable to devise a device, assembly and/or method useful inaltering and/or reshaping the annulus of the mitral valve and/or theventricle of a heart without the need to gain access to the interior ofthe heart, and which can be adjusted after fixation to the heart toalter and/or reshape the annulus and/or ventricular geometry so as tomaintain satisfactory abatement or reduction of mitral regurgitation.

It may further be desirable to provide devices that can be minimallyinvasively implanted and/or which allow procedural reversibility and/oradjustment.

SUMMARY OF THE INVENTION

The present invention relates to a system for valve repair thatdecreases the diameter of the heart in the septal lateral directionand/or anterior posterior direction and brings the leaflets of a valveback to a normal anatomical position. The system does this by gentlysqueezing from the surface of the heart using a multi-step deliverymethod which may optionally use a multi-step delivery system to implantan epicardial device.

In one aspect of the present invention, an epicardial device forreducing or preventing regurgitation of blood through a valve of a heartis provided that includes: a main body having a segment adapted to applyforce to an epicardial surface of the heart; a member that appliescounterforce to said force applied by the segment; a foundationconfigured to be anchored to the epicardial surface of the heart, thefoundation comprising a surface configured with attachment features; andthe device further including a surface configured with mating attachmentfeatures configured to attach to the attachment features of thefoundation; wherein the mating attachment features and attachmentfeatures are separable and reattachable to allow repositioning of atleast a portion of the device relative to the foundation.

In at least one embodiment, the epicardial device includes a flapextending from the segment, the flap including a mating surfaceconfigured with the mating attachment features.

In at least one embodiment, the segment comprises a rigid structural ribcontained within a pad; wherein the pad comprises a contact surfaceconfigured to apply the force to the epicardial surface.

In at least one embodiment, the segment comprises a pad; wherein the padcomprises a contact surface configured to apply the force to theepicardial surface; and wherein the flap extends inferiorly from thepad.

In at least one embodiment, the pad is configured to apply force to aposterior surface of the heart at a location superior to a locationwhere the foundation is configured to be anchored.

In at least one embodiment, a rigid structural rib is contained withinthe pad.

In at least one embodiment, the flap is reattachable to the foundationto change a distance between the foundation and the segment.

In at least one embodiment, the epicardial device is configured forreshaping an annulus of a mitral valve of the heart.

In at least one embodiment, the epicardial device is configured forreshaping one or more dimensions of a left ventricle of the heart.

In at least one embodiment, the epicardial device is configured forreshaping an annulus of a tricuspid valve of the heart.

In at least one embodiment, the epicardial device is configured forreshaping one or more dimensions of a right ventricle of the heart.

In at least one embodiment, the segment comprises a posterior segmentadapted to be contacted to a posterior surface of the heart, the membercomprises an anterior segment configured to be contacted to an anteriorsurface of the heart, and the main body further comprises a lateralsegment joining the anterior segment and the posterior segment.

In at least one embodiment, an annulus of a mitral valve lies in a planebetween a left atrium and a left ventricle of the heart, the anatomy ofthe heart includes an aorta, a pulmonary trunk, a superior vena cava, atransverse sinus, an oblique sinus, and an atrioventricular groove; theanterior segment is configured to be positioned in the transverse sinusof the heart; the posterior segment is configured to be positioned on orinferior to the atrioventricular groove of the heart; and the lateralsegment extends between the anterior segment and the posterior segment.

In at least one embodiment, the foundation comprises a first foundation,the epicardial device further comprising a second foundation, whereinthe second foundation is configured to be anchored to the epicardialsurface of the heart at a location inferior to a location where thefirst foundation is configured to be anchored; the second foundationcomprising a second surface configured with second attachment features;and the device further comprising a surface configured with secondmating attachment features configured to attach to the second attachmentfeatures of the second foundation; wherein the second mating attachmentfeatures and second attachment features are separable and reattachableto allow repositioning of at least a second portion of the devicerelative to the second foundation.

In at least one embodiment, the epicardial device includes a flapextending from the segment and an extension extending from one of thesegment or the flap; wherein the extension is reattachable to the secondfoundation to change a distance between the second foundation and thefirst foundation.

In at least one embodiment, the epicardial device further includes athird foundation, wherein the third foundation is configured to beanchored to the epicardial surface of the heart at a location inferiorto a location where the first foundation is configured to be anchoredand separate from a location where the second foundation is configuredto be anchored; the third foundation comprising a third surfaceconfigured with third attachment features; and the device furthercomprising a surface configured with third mating attachment featuresconfigured to attach to the third attachment features of the thirdfoundation; wherein the third mating attachment features and thirdattachment features are separable and reattachable to allowrepositioning of at least a third portion of the device relative to thethird foundation.

In at least one embodiment, the epicardial device includes a flapextending from the segment and a first extension extending from one ofthe segment or the flap; and a second extension extending from one ofthe segment or the flap; wherein the first extension is reattachable tothe second foundation to change a distance between the second foundationand the first foundation; and wherein the second extension isreattachable to the third foundation to change a distance between thethird foundation and the first foundation.

In another aspect of the present invention, an epicardial device forplacement on the epicardial surface of a heart in order to reshape theannulus of the mitral valve of the heart is provided, the mitral valvelying in a plane between the left atrium and the left ventricle of theheart, the anatomy of the heart includes an aorta, a pulmonary trunk, asuperior vena cava, a transverse sinus, and an atrioventricular groove.The epicardial device includes: an anterior segment, a posterior segmentand a lateral segment extending between the anterior segment and theposterior segment; wherein the anterior segment is configured anddimensioned to at least partially occupy the transverse sinusepicardially; wherein the lateral segment is configured for positioningthe anterior segment on or above a plane in which the mitral valve islocated, and the posterior segment on or below the plane in which themitral valve is located, and below a position of the anterior segment;wherein the posterior segment is configured to apply a force to aposterior epicardial surface of the heart; a foundation configured to beanchored to the posterior epicardial surface of the heart, thefoundation comprising a surface configured with attachment features; andthe device further comprising a surface configured with matingattachment features configured to attach to the attachment features ofthe foundation; wherein the mating attachment features and attachmentfeatures are separable and reattachable to allow repositioning of atleast the posterior segment relative to the foundation.

In at least one embodiment, the epicardial device includes a flapextending from the posterior segment, the flap comprising a matingsurface configured with the mating attachment features, wherein the flapis attachable, detachable and reattachable to and from the foundation toaffect a change in position of at least the posterior segment relativeto the foundation when the foundation is anchored.

In at least one embodiment, the foundation comprises a first foundation,the epicardial device further comprising a second foundation, whereinthe second foundation is configured to be anchored to the epicardialsurface of the heart at a location inferior to a location where thefirst foundation is configured to be anchored; the second foundationcomprising a second surface configured with second attachment features;and the device further comprising a surface configured with secondmating attachment features configured to attach to the second attachmentfeatures of the second foundation; wherein the second mating attachmentfeatures and second attachment features are separable and reattachableto allow repositioning of at least a second portion of the devicerelative to the second foundation.

In at least one embodiment, the epicardial device includes a flapextending from the segment and an extension extending from one of theposterior segment or the flap; wherein the second foundation isconfigured to be attached to the epicardial surface of the heart;wherein the extension is reattachable to the second foundation to applyforces to the epicardial surface to reduce tension on chordae tendineaeof the heart.

In at least one embodiment, the epicardial device further includes athird foundation, wherein the third foundation is configured to beanchored to the epicardial surface of the heart at a location inferiorto a location where the first foundation is configured to be anchoredand separate from a location where the second foundation is configuredto be anchored; the third foundation comprising a third surfaceconfigured with third attachment features; and the device furthercomprising a surface configured with third mating attachment featuresconfigured to attach to the third attachment features of the thirdfoundation; wherein the third mating attachment features and thirdattachment features are separable and reattachable to change forceapplied between the third foundation and the posterior segment.

In another aspect of the present invention, a method of epicardialtreatment of valve regurgitation associated with a valve of a heart of apatient includes: establishing at least one opening in the patient toprovide access to the heart; applying an epicardial force on a locationof the heart, while visualizing regurgitation through the valve viavisualization apparatus; varying at least one of the location or theamount of epicardial force applied to identify a target position wherevalve regurgitation is reduced or eliminated; marking the targetposition; anchoring a foundation to the epicardial surface of the heartto provide a base for fixing an epicardial device thereto; and fixingthe epicardial device to the foundation, wherein the fixing establishesa segment of the device in the target position and wherein the fixingindirectly fixes the epicardial device to the heart.

In at least one embodiment, the method includes visualizing functioningof the valve after the fixing the epicardial device; detaching theepicardial device from the foundation when the further visualizing showsan unacceptable amount of regurgitation; repositioning the epicardialdevice to reduce the amount of regurgitation and verifying reduction inregurgitation by the further visualizing; and re-attaching theepicardial device to the foundation.

In at least one embodiment, the foundation comprises a first foundation,and the method further includes: anchoring a second foundation to theepicardial surface of the heart; and attaching an extension between thesecond foundation and one of the first foundation or the segment toapply compression forces between the second foundation and the one ofthe first foundation or the segment to reduce tension on chordaetendineae of the heart.

In at least one embodiment, the valve is the mitral valve, the segmentcomprises a posterior segment, the epicardial device further comprisesan anterior segment, an anterior end, a posterior end and a lateralsegment extending between the anterior segment and the posteriorsegment; wherein the anterior and posterior segments are positionedepicardially on the heart at locations apposite to an annulus of themitral valve, such that the anterior and posterior segments apply forcesufficient to reshape the annulus.

In at least one embodiment, the method further includes: measuring adistance between opposing epicardial surfaces of the heart where one ofthe opposing epicardial surfaces is measured at the target position; andselecting the epicardial device so that the epicardial device isconfigured with opposed force applying segments separated by a distancethat approximates the measured distance between the opposing epicardialsurfaces, when the epicardial device is installed on the heart and fixedto the foundation.

In at least one embodiment, the method further includes: measuring anunobstructed length of a transverse sinus of the heart; and providingthe epicardial device to have an anterior segment length less than orequal to the unobstructed length, wherein the anterior segment ispositioned in the transverse sinus prior to the fixing.

In another aspect of the present invention, a method of epicardialtreatment of mitral valve regurgitation associated with a mitral valveof a heart of a patient is provided, the anatomy of the heart includingan aorta, a pulmonary trunk, a superior vena cava, a transverse sinus, aleft atrial appendage, and an oblique sinus. The method includes:applying an epicardial force on a posterior location of the heart, whilevisualizing regurgitation through the valve via visualization apparatus;varying at least one of the location or the amount of epicardial forceapplied to identify a target position where mitral valve regurgitationis reduced or eliminated;

marking the target position; lifting the heart at least partially out ofa chest cavity of the patient to allow direct visualization of themarking; anchoring a foundation to the epicardial surface of the heartat a location having a predefined relationship to the marking; providinga clip having an anterior segment, an anterior end, a posterior segment,a posterior end and a lateral segment extending between the anteriorsegment and the posterior segment; positioning the anterior andposterior segments epicardially on the heart at locations apposite to anannulus of the mitral valve, such that the anterior and posteriorsegments apply force sufficient to reshape the annulus, wherein theposterior segment is located on the target position; fixing the clip tothe foundation, wherein the fixing maintains the posterior segment inthe target position.

In at least one embodiment, the anterior segment is at least partiallyinserted into a transverse sinus of the heart and the transverse sinusmaintains a position of the anterior segment.

In at least one embodiment, the method further includes: lowering theheart to return it to a position in the chest cavity; furthervisualizing functioning of the mitral valve; detaching the clip from thefoundation to allow repositioning the clip to reduce an amount of mitralregurgitation; repositioning the clip to reduce the amount ofregurgitation and verifying reduction in regurgitation by the furthervisualizing; and re-attaching the clip to the foundation.

In at least one embodiment, the method further includes: anchoring asecond foundation to the epicardial surface of the heart at a secondlocation; attaching an extension to the second foundation, the extensionextending from one of the foundation or the clip, to establish acompression force between the second foundation and the one of thefoundation or the clip, to reduce tension on chordae tendineae of theheart.

In at least one embodiment, the method further includes: lowering theheart to return it to a position in the chest cavity; detaching theextension from the second foundation; and re-attaching the extension tothe second foundation in a relative position to vary the amount ofreduction in tension on the chordae tendineae.

In another aspect of the present invention, a minimally invasive methodfor epicardial implantation of a device for treatment of valveregurgitation, is provided, the method including: installing a deviceport, a camera port and at least one instrument port in the chest of apatient to permit access to a chest cavity of the patient by the device,a camera and instruments; insufflating the chest cavity; positioning thecamera though the camera port and into the chest cavity; introducing afoundation through one of the ports; anchoring the foundation to anepicardial surface of the heart; introducing the device through thedevice port and into the chest cavity using an instrument controlledfrom outside the chest cavity and device port; manipulating the deviceto partially surround an annulus of a valve by placement of the deviceon epicardial walls of the heart at locations that partially surroundthe annulus; and anchoring the device to the epicardial walls of theheart at least in part by attaching a portion of the device to theanchored foundation.

In at least one embodiment, the method further includes: prior tointroducing the foundation, assessing a width measurement for selectinga device having opposing contact surfaces defining a width that mostclosely matches the width measurement wherein the assessing comprises:passing a width measuring instrument through the device port;positioning and manipulating the width measuring instrument to applyforces to an epicardial surface of the heart in a plane of the valve tobe treated, while visualizing functioning of the valve to assess anyregurgitation that may be occurring; repositioning the width measurementinstrument and/or varying an amount of force applied by the widthmeasurement instrument while continuing said visualizing; identifying alocation where the width measurement instrument is applied to theepicardial surface where regurgitation is minimized or eliminated.measuring the width between the location, as presently deformed by thewidth measurement instrument in the identified location, with a forceused at the identified location to establish the minimization orelimination of regurgitation and a location opposite the identifiedlocation, on an opposite epicardial surface; removing the widthmeasuring instrument from the chest cavity, out of the device port; andselecting the device having opposing contact surfaces defining a widththat most closely matches the width measurement.

In at least one embodiment, the foundation is attached at a locationhaving a predefined relationship relative to the identified location.

In at least one embodiment, the valve being treated is a mitral valve,and the method includes: prior to introducing the device, assessing ananterior-posterior dimension of a transverse sinus of the heart, whereinthe assessing includes: inserting a length sizing instrument through oneof the ports with a manipulating instrument operated from outside of theport; manipulating the length sizing instrument with the manipulatinginstrument to insert the length sizing instrument into the transversesinus; inserting the length sizing instrument to extend over a usablelength of the transverse sinus that does not include an obstruction;reading a length measured by the length sizing instrument when fullyinserted in the usable length; removing the length sizing instrumentfrom the chest cavity; and selecting the device that has an anterior armhaving a best match to the length measured.

In at least one embodiment, the reading comprises grasping the lengthsizing instrument with an instrument and reading a measurement along agradient scale on the length sizing instrument, using the camera,wherein the reading is taken at a location where the length sizinginstrument is at an open end of the transverse sinus.

In at least one embodiment, the valve being treated is a tricuspidvalve.

These and other advantages and features of the invention will becomeapparent to those persons skilled in the art upon reading the details ofthe devices and methods as more fully described below.

BRIEF DESCRIPTION OF THE DRAWINGS

In the course of the detailed description to follow, reference will bemade to the attached drawings. These drawings show different aspects ofthe present invention and, where appropriate, reference numeralsillustrating like structures, components, materials and/or elements indifferent figures are labeled similarly. It is understood that variouscombinations of the structures, components, materials and/or elements,other than those specifically shown, are contemplated and are within thescope of the present invention.

FIG. 1A is a posterior, perspective view of an epicardially implantabledevice, according to an embodiment of the present invention.

FIG. 1B shows the opposite surface of the flap shown in FIG. 1A.

FIGS. 1C and 1D illustrate the flap and foundation of FIG. 1A providedwith alternative attachment features, according to an embodiment of thepresent invention.

FIG. 2 is an anterior, perspective view of the device clip shown in FIG.1A.

FIGS. 3A-3B are illustrations of a human heart, with the illustration inFIG. 3B viewed with the pericardium removed.

FIG. 4A is an anterior view of a human heart, with the device placed onthe epicardial surface of the heart, according to an embodiment of thepresent invention.

FIG. 4B is a posterior view of the heart shown in FIG. 4A with thedevice placed on the epicardial surface of the heart, according to anembodiment of the present invention.

FIG. 5 is a top view of the ventricular portion of the heart with deviceshown in FIGS. 4A-4B, with the atria removed to shown the mitral valve.

FIG. 6A. illustrates an anterior view of a human heart.

FIG. 6B illustrates a posterior view of the heart of FIG. 6A.

FIG. 7A shows an echocardiogram illustrating occurrence of severe mitralvalve regurgitation during systole.

FIG. 7B shows an echocardiogram illustrating occurrence of moderatemitral valve regurgitation during systole.

FIG. 7C shows an echocardiogram illustrating occurrence of mild mitralvalve regurgitation during systole.

FIG. 7D shows an echocardiogram where no mitral valve regurgitationoccurs during ventricular systole.

FIG. 8 illustrates an echocardiogram taken in a plane (or approximatinga plane) of the mitral valve annulus, according to an embodiment of thepresent invention.

FIG. 9 is a view of a width sizing instrument with a view of the contactsurface, according to an embodiment of the present invention.

FIG. 10 is a schematic illustration of application of force through awidth sizing instrument to the posterior surface of the heart, accordingto an embodiment of the present invention.

FIG. 11 is a schematic illustration of anchoring a foundation to theepicardial wall of the posterior side of the heart, according to anembodiment of the present invention.

FIG. 12 illustrates the device clip having been installed on the heart,and the flap having been attached to the foundation, according to anembodiment of the present invention.

FIG. 13 illustrates a number of events that can be carried out in amethod of implanting a device according to an embodiment of the presentinvention.

FIGS. 14A-14C are perspective and plan views of a length sizinginstrument, according to an embodiment of the present invention.

FIG. 15 illustrates insertion of a length sizing device into thetransverse sinus of a heart of a patient to be treated for mitral valveregurgitation, according to an embodiment of the present invention.

FIG. 16A is a posterior, perspective view of an epicardially implantabledevice according to another embodiment of the present invention.

FIG. 16B is an isolated view of anterior surface of an extension of thedevice of FIG. 16A.

FIG. 17 is a variant of the device of FIG. 16A.

FIG. 18 is a cutaway view of a human heart illustrating chordaetendineae and papillary muscles in the left and right ventricles.

FIG. 19 is an isolated view showing attachment of the papillary musclesto the anterior leaflet and posterior leaflet of the mitral valve viachordae tendineae.

FIG. 20 is a partial, sectional view of a heart illustrating the deviceof FIG. 16A having been epicardially installed thereon for treatment ofmitral valve regurgitation, according to an embodiment of the presentinvention.

FIG. 21 illustrates a number of events that can be carried out in amethod of implanting a device according to an embodiment of the presentinvention.

FIG. 22 illustrates events that may be carried out in the performance ofa minimally invasive procedure for epicardial implantation of a devicefor treatment of valve regurgitation according to an embodiment of thepresent invention.

FIG. 23 illustrates locations of port placement in a patient for aprocedure according to an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Before the present devices and methods are described, it is to beunderstood that this invention is not limited to particular embodimentsdescribed, as such may, of course, vary. It is also to be understoodthat the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to be limiting, sincethe scope of the present invention will be limited only by the appendedclaims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimits of that range is also specifically disclosed. Each smaller rangebetween any stated value or intervening value in a stated range and anyother stated or intervening value in that stated range is encompassedwithin the invention. The upper and lower limits of these smaller rangesmay independently be included or excluded in the range, and each rangewhere either, neither or both limits are included in the smaller rangesis also encompassed within the invention, subject to any specificallyexcluded limit in the stated range. Where the stated range includes oneor both of the limits, ranges excluding either or both of those includedlimits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the present invention, the preferred methodsand materials are now described. All publications mentioned herein areincorporated herein by reference to disclose and describe the methodsand/or materials in connection with which the publications are cited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. Thus, for example, reference to “atack” includes a plurality of such tacks and reference to “thefoundation” includes reference to one or more foundations andequivalents thereof known to those skilled in the art, and so forth.

The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application. Thedates of publication provided may be different from the actualpublication dates which may need to be independently confirmed.

Definitions

As used in the specification and the appended claims, the term“anterior” is used in its anatomical sense to mean “toward the front, infront of, or the front surface of.”

As used in the specification and the appended claims, the term“posterior” is used in its anatomical sense to mean “toward the back, inback of, or the back surface of.”

As used in the specification and the appended claims, the term“superior” is used in its anatomical sense to mean “above, over top of,directed upward or toward the head.”

As used in the specification and the appended claims, the term“inferior” is used in its anatomical sense to mean “below, underneath,directed downward or toward the feet.”

As used in the specification and the appended claims, the term “lateral”is used in its anatomical sense to mean “a position or direction fartherfrom the sagittal or median plane or midline of the body, to the sideof, or the side surface of.”

Detailed Description

Devices, apparatus and methods are provided for implantation to reducethe size of an annulus to correct coaptation of valve leaflets withinthe annulus that have been rendered dysfunctional by an enlargement ofthe annulus. In at least one embodiment, an epicardial clip forplacement on the epicardial surface of a heart in order to reshape theannulus of the mitral valve of the heart is provided, the mitral valvelying in a plane between the left atrium and the left ventricle of theheart, the anatomy of the heart includes an aorta, a pulmonary trunk, asuperior vena cava, a transverse sinus, and an atrioventricular groove.

Epicardial devices, when implanted may apply force to both anterior andposterior (and potentially, lateral) surfaces of the heart to translatethese forces for the desired reshaping of the annulus and/or ventricle.Methods described herein may include an observation stage during whichmanual force is applied to a posterior surface of the heart, while usingvisualization techniques to determine a target location and amount offorce (resulting in an amount of deformation of the heart wall) that issufficient to eliminate or satisfactorily reduce an amount ofregurgitation through the valve leaflets that an annulus affected by thedeformation surrounds. This observation stage may be used to determine asize of an implant to be implanted, as well as the position (targetlocation) on the posterior surface of the heart that the posteriorsegment of the device is to be implanted. The heart can then be liftedup and partially out of the chest cavity, so that the posterior segmentcan be implanted in the target location that has been identified. Thisposes potential problems, as it is often difficult to observe the exactlocation or footprint of the application of force to the posteriorsurface. Even when an accurate observation of the footprint can be made,it still may be difficult to accurately locate the posterior portion ofthe device on the footprint, as it is difficult, if not impossible todirectly visualize the placement of the device relative to the posteriorsurface. Once the posterior portion/segment is attached and the heart isrepositioned to its original location, there may therefore be a greateramount of regurgitation occurring than what was observed during theobservation stage. In such instances, this may require a repositioningof the posterior segment to a more optimal location that further reducesregurgitation, or in worse cases, complete replacement of the implant byan implant having a different width dimension between the anterior andposterior segments than that which was originally used. In either case,the repositioning or replacement of the posterior segment/implantinvolves removing screws, tacks or other fixation means that were usedto fix the original posterior segment, and then reattachment of theposterior segment or replacement posterior segment, again with screws,tacks or other fixation means. The removal of the fixation means resultsin bleeding from the heart wall, which can cause further complicationsto the procedure, not limited to decreased visibility for continuingsteps in the procedure, increased risk of infection, and/or longerhealing times. The present invention eliminates these risks and providesthe surgeon with the ability to anchor and adjust the posterior portionof the implant with much greater ease, safety and with a significantreduction in the time than would be otherwise required forre-implantation/repositioning as described. Such adjustment can beperformed even after anchoring the device epicardially to the heart,thereby eliminating the need to remove and implant and reinstall it witha different or reconfigured implant. This also eliminates the need toremove tissue anchors. Still further, the present invention allowsprocedures, after completion of implantation, to reenter the target siteto manually adjust the device to change the location of the posteriorsegment and thereby alter the direction of the force and possibly theamount of force as applied thereby, to restore the successful reductionor elimination of valve regurgitation. With these procedures, it is notnecessary to remove the device or even to remove the tissue anchors.

FIG. 1A is a posterior, perspective view of an epicardially implantabledevice 10 according to an embodiment of the present invention. In thisembodiment, device 10 may have a generally U-shape or C-shape whenviewed from a top or bottom view, and which can also be seen in thisperspective orientation. The device 10 may be shaped such that thedistance 160 across the device 10A between the contact surface of theanterior segment 162 and the contact surface of the posterior segment164 defines the space between which the mitral valve and mitral valveannulus (as well as the heart walls apposite these features) will belocated after implantation of the device 10 and may determine the finalanterior-posterior diameter of the mitral valve annulus. The anteriorsegment 162 may be substantially straight, and thus capable of residingin the transverse sinus of the heart. The posterior segment 164 may bearcuate, corresponding to the convex curvature of the posteriorventricular wall of the heart in a location where it is designed to bepositioned for implantation. The lateral segment 166 interconnects theanterior 162 and posterior 164 segments with a sufficient length toestablish the appropriate distance 160 between the segments 162 and 164for effectively applying force to the mitral valve annulus 22A to causea reduction or elimination of mitral valve regurgitation. The main bodyor frame 202 of device 10 extends through all segments 162, 164 and 166and is non-flexible and rigid to an extent wherein the conformationshown is not readily deformed and is not deformed by the forces appliedto it by the beating heart when it is implanted. In this embodiment,frame 202 is formed by a metal wire, preferably out of titanium ortitanium alloy, but could alternatively be formed from otherbiocompatible metals such as stainless steel, such as 304V, 304L, and316LV stainless steel; mild steel; nickel-titanium alloy such aslinear-elastic and/or super-elastic nitinol; other nickel alloys such asnickel-chromium-molybdenum alloys, and the like.

The posterior segment 164 in this embodiment includes a pad 56 which ispreferably compliant and is atraumatic when contacted to target tissuesuch as the heart. Pad 56 may be formed as an over-mold of silicone orother compliant, biocompatible material. Pad 56 encases at least aportion of, preferably substantially the entire posterior segmentportion of the frame (rod) 220. Pad 56 is preferably made from silicone,but could alternatively be made from other moldable, biocompatiblepolymers. Alternatively, device 10 may be provided with the posteriorsegment 164 having no pad, so that the main frame 202 forms theposterior segment 164. Further alternatively, the pad 56 may beencapsulated by a sheath 57, or, if the pad 56 is not included, the mainframe 202 of the posterior segment may be encapsulated by a sheath 57.Still further alternatively, all segments 162, 164 and 166 may beencapsulated by a sheath 57A with or without presence of the pad 56. Insome embodiments, for example, sheath 57 may be an ePTFE material,non-molded fluorinated ethylene propylene (FEP), a polyester knittedfabric, a polyester velour, a polypropylene felt, a woven or braidedfabric, a non-woven fabric, porous material, or other textile material,as desired. Sheath 57 may promote tissue in-growth on the epicardialsurface of the heart, may provide tissue in-growth into interstices ofthe fabric sheath 133, and/or provide adequate frictional forces(traction) to hold the clip 110 in contact with the heart and preventmigration of the device once positioned on the heart. Tissue in-growththerein and/or thereon may provide long-term retention of the clip 110in a desired position on the heart and prevent erosion.

In some embodiments, device 10 may include a drug eluting coating inaddition to or as an alternative to sheath 57. The drug eluting coatingmay a controlled release of a therapeutic agent over a specified periodof time. The therapeutic agent may be any medicinal agent which mayprovide a desired effect. Suitable therapeutic agents include drugs,genetic materials, and biological materials. Some suitable therapeuticagents which may be loaded in the drug eluting coating include, but arenot necessarily limited to, antibiotics, antimicrobials, antioxidants,anti-arrhythmics, cell growth factors, immunosuppressants such astacrolimus, everolimus, and rapamycin (sirolimus), therapeuticantibodies, wound healing agents, therapeutic gene transfer constructs,peptides, proteins, extracellular matrix components, steroidal andnon-steroidal anti-inflammatory agents, anti-proliferative agents suchas steroids, vitamins and restenosis inhibiting drugs, such as Taxol®,paclitaxel (i.e., paclitaxel, paclitaxel analogues, or paclitaxelderivatives, and mixtures thereof).

A flap 85 extends inferiorly from the pad 56 of posterior portion 164 inthe embodiment of FIG. 1A. Flap 85 functions to anchor the posteriorportion 164 to the posterior wall of the heart by attachment tofoundation 185 as described in more detail below. Flap 85 may be formedintegrally with pad 56 and may be of the same or different material.Typically the flap is made of a material described above for use inmaking sheath 57. Flap 85 may be attached directly to the main frame 202in embodiments where a pad 56 is not employed. Flap 85 may bemanufactured separately and then mechanically and/or chemically fixed topad 56 or main frame 202.

A foundation 185 is separately provided and is configured to beimplanted to the surface of the heart, such as by anchoring using tacks,screws or other equivalent fixation means. Foundation 185 is a thinstructure that can be fixed to the heart wall prior to anchoring theposterior segment 164. For example, foundation 185 may be made from athin layer of silicone or other structural core layer to providestructure thereto, which may then be covered with any of the samematerials described above for use in making sheath 57. Alternativematerials could be used that are biocompatible and flexible, but whichhave sufficient rigidity to provide structural support to thefoundation, such that it can be deformed to conform to the curvature ofthe surface of the heart that it is being anchored to, but retainssufficient rigidity so that it does not buckle, wrinkle, or otherwisedeform from its conforming shape. Optionally that core of the foundationmay not be covered. For example, when the desired target location forfixation of the posterior segment is identified (described in moredetail below), the foundation can then be implanted on the heart wall ina location that will fix the posterior segment in the target locationwhen flap 85 is attached to foundation 185. To establish the attachmentof flap 85 to foundation 185, the surfaces of the flap 85 and foundation185 that come into contact with one another to accomplish the attachmentare provided with mating attachment features 85A, 185A.

In the embodiment of FIGS. 1A-1B the attachment features arehook-and-loop type fasteners, such as VELCRO®, with the hook typefeatures provided as 185A and the loop type features provided as 85A.Alternatively, 85A could be hook type features and 185A could be looptype features. FIG. 1B shows the reverse surface of the flap 85 shown inFIG. 1A, which is the surface that interfaces with the outer surface ofthe foundation (faces outwardly from the heart surface when foundation185 is implanted on the heart surface), shown in FIG. 1A. The surfacearea of the outer surface of foundation 185 may be equal to, less thanor greater than the surface area of the surface of flap 85 that itinterfaces with. Preferably, the superior-inferior dimension 185I offoundation 185 is greater than the superior-inferior dimension 85I tobetter support adjustment of the flap 85 in the inferior-superiordirection relative to the foundation 185, although this is notnecessary. In FIG. 1A the hooks of the hook type fasteners face in theinferior direction to facilitate movement of the flap 85 inferiorlyrelative to the foundation 185 so that less force is required foradjustment movement in that direction. However, the hook orientationscould alternatively face superiorly, laterally, in any directions, inmultiple directions, or randomly. Further alternatively, other types ofattachment features may be substituted that still attach the flap 85 andfoundation 185 with sufficient holding force to maintain the flap 85 andfoundation 185 fixed with respect to one another over the lifetime ofthe implantation, as do the hook and loop type fasteners, but also allowthe surgeon (or other operator) to manually detach the flap from thefoundation and reattach the flap 85 to the foundation 185, if needed,without the requirement of removing any attachment features from thetissue of the heart. Examples of such alternatives include, but are notlimited to: magnets, restickable glue, multiple rows of snaps, or thelike. FIGS. 1C and 1D show another alternative arrangement in which theflap 85 is provided with a bar or rod 85A spaced from the surface of theflap 85 to allow it to be captured by hooks 185A mounted on foundation185 as illustrated in FIG. 1D. In this embodiment, the flap 85 can bepositioned in one of three different rows of hooks 185A to vary theinferior/superior position of the flap 85 relative to the foundation185. Of course, this embodiment is not limited to three rows of hooks,as two rows or more than three rows could be incorporated.

The lengths and orientations of the anterior 162, posterior 164 andlateral 166 segments may include any of those described in US PatentApplication Publication No. 2012/0323314 which is hereby incorporatedherein, in its entirety, by reference thereto. For example, the length56L of the posterior segment 164 may be in the range of 25 mm to 80 mm,in the range of 31 to 70 mm, in the range of 38 mm to 64 mm, or in therange of about 39 mm to about 64 mm, in some instances in the range from30 mm to 40 mm, from 40 mm to 50 mm, from 45 mm to 55 mm, from 33 mm to37 mm, from 43 mm to 47 mm, from 48 mm to 53 mm, in some instances 30mm, 35 mm, 40 mm, 45 mm or 50 mm. The width of the posterior segment/pad56W may be in the range of 5 mm to 30 mm, in the range of 8 mm to 25 mm,in the range of 10 mm to 20 mm, or 12 mm to 18 mm or 13 mm to 17 mm or14.5 to 15.5 mm in some instances. The posterior segment 164 may have aradius of curvature extending along the length thereof that is variableand designed to conform to the contour of the heart wall against whichit is intended to apply force. The largest radius of curvature along thelength direction of the contact surface (surface of 164 facing into pagein FIG. 1A) may be in the range of 50 mm to 130 mm, 40 mm to 115 mm, 75mm to 105 mm, or about 73 mm to 104 mm in some instances.

The anterior segment 162 has a length 162L designed so that the anteriorsegment 162 can be received in the transverse sinus, and so that withthe lateral segment 166 contacting the surface of the heart, the freeend of anterior segment 162 extends as far into the transverse sinus aspossible without obstructing a pulmonary vein or other structure thatcould be extending into the transverse sinus. Anterior segment 162, maybe a straight segment, such as illustrated in FIG. 1A and length 162Lmay be in the range from 40 mm to 80 mm, in the range from 45 mm to 50mm, in the range from 50 mm to 55 mm, 55 mm to 60 mm, 60 mm to 65 mm, 65mm to 72 mm, 72 mm to 80 mm or in the range from 40 mm to 85 mm in someinstances. In one specific, non-limiting embodiment, at least twodevices 10 are provided in a kit, the first device having a length 162Ldifferent from a length 162L of a second device 10 and the first andsecond devices have equal width measurements 160. In anothernon-limiting embodiment, at least two devices 10 are provided in a kit,the first device having a length 162L equal to a length 162L of a seconddevice 10 and the first and second devices have unequal widthmeasurements 160. In another non-limiting embodiment, at least twodevices 10 are provided in a kit, the first device having a length 162Ldifferent from a length 162L of a second device 10 and the first andsecond devices have unequal width measurements 160. In one specific,non-limiting embodiment, at least two pairs of devices 10 are providedwherein a first pair has equal width measurements 160 and unequal lengthmeasurements, and the second pair has equal width measurements 160 toeach other (but unequal to the width measurement 160 of the first pair)and unequal length measurements. 162L. In at least one embodiment, theunequal length measurements 162L are also unequal to each of the lengthmeasurements 162L of the second pair. In at least one embodiment, atleast one of the unequal measurements 162L is equal to one of theunequal measurements 162L of the second pair. More than a pair ofdevices 10 having the same width measurement 160 may be provided, witheach having a length measurement 162L different from the others. Morethan two different width 160 sizes of devices may also be provided,wherein multiple ones of each particular width size 160 each have adifferent length 162L: In one specific example, two devices 10 having awidth of 35 mm were provided with a first of these devices 10 having alength 162L of 55 mm and the second having a length of 48 mm; twodevices 10 having a width of 40 mm were provided with a first of thesedevices 10 having a length 162L of 63 mm and the second having a lengthof 56 mm; two devices 10 having a width of 45 mm were provided with afirst of these devices 10 having a length 162L of 70 mm and the secondhaving a length of 63 mm; and two devices 10 having a width of 50 mmwere provided with a first of these devices 10 having a length 162L of78 mm and the second having a length of 70 mm. Optionally, a thirddevice 10 having a width of 50 mm had a length 162L of 63 mm.

Flap 85 extends inferiorly from the pad 56 or main body 202 by adistance 85I that, together with the length 85L establishes a surfacearea sufficient to mate with the opposing surface area 185 in an amountsufficient to fix the components together so that they remained fixedunless the surgeon/installer purposely separates them for readjustmentor replacement. For example the length 85L may be about the same orslightly less than length 56L, but need not be, as it could be much lessthan 56L. Width 85I is typically less than length 85L, typically in arange from about 30% to 90% of length 85L, more typically from about 40%to 70% of length 85L, although width values may vary from these typicalranges. The width 185I of foundation 185 may be in a range from about25% to 200% of width 85I, but is typically about the same as width 85I.Preferably, the superior-inferior dimension 185I of foundation 185 isgreater than the superior-inferior dimension 85I to better supportadjustment of the flap 85 in the inferior-superior direction relative tothe foundation 185, although this is not necessary. Typically theattachment features are strong enough in shear strength so that the sizeof the foundation 185 does not have to be greater than the size of theflap 85. The surface area of the flap 85 where attachment features areattached to mating attachment features on the foundation 185 needs to belarge enough to provide sufficient shear strength by the matingattachment features, so that forces thereagainst by the posterior arm164 pulling upward toward the transverse sinus and away from the apex ofthe heart does not overcome the shear strength of the mating attachmentfeatures.

Device 10 may be configured so that the lateral segment 166 can berouted around the left lateral side of the heart, placing the anteriorsegment 162 in the transverse sinus and the posterior segment 164 on theposterior of the heart, such as on or inferior to the atrioventriculargroove or in the oblique sinus of the heart. In some embodiments thelateral segment 166 may be routed around, over and/or under the leftatrial appendage of the heart. In other embodiments, the lateral segment166 may be routed over the left atrium of the heart.

In some variants of this and all other embodiments described herein, thedevice may include a drug eluting coating in addition to pad 56. Thedrug eluting coating may be provided in addition to a sheath or as analternative to the sheath. The drug eluting coating may a controlledrelease of a therapeutic agent over a specified period of time. Thetherapeutic agent may be any medicinal agent which may provide a desiredeffect. Suitable therapeutic agents include drugs, genetic materials,and biological materials. Some suitable therapeutic agents which may beloaded in the drug eluting coating include, but are not necessarilylimited to, antibiotics, antimicrobials, antioxidants, anti-arrhythmics,cell growth factors, immunosuppressants such as tacrolimus, everolimus,and rapamycin (sirolimus), therapeutic antibodies, wound healing agents,therapeutic gene transfer constructs, peptides, proteins, extracellularmatrix components, steroidal and non-steroidal anti-inflammatory agents,anti-proliferative agents such as steroids, vitamins and restenosisinhibiting drugs, such as TAXOL®, paclitaxel (i.e., paclitaxel,paclitaxel analogues, or paclitaxel derivatives, and mixtures thereof).

Pad 56 includes a contact surface 56C (see anterior, perspective view ofFIG. 2) that is configured to contact a posterior surface of the heartwhen implanted, according to this embodiment and all other embodiments.The contact surface 56C is preferably curved (but is not necessarilycurved in all embodiments) to follow a contour of a posterior surface ofthe heart at a location where it is designed to be implanted. Allcorners and ends of the pad may be rounded or otherwise structured so asto be atraumatic to surrounding tissues during and after implantation ofthe device 10. The anterior segment 162 is configured and dimensioned toat least partially occupy the transverse sinus epicardially and end at alocation short of overlying the right atrium; the lateral segment 166being curved so that the anterior segment 162 can be positioned on orabove a plane in which the mitral valve is located, which allows aportion of the posterior segment 164 to be positioned on or below theplane in which the mitral valve is located, wherein rotation of thedevice 10 about a longitudinal axis of the anterior segment 162 allowsthe posterior segment 164 to be moved towards or away from the apex ofthe heart while the anterior segment 162 remains in full contact with abase of the transverse sinus, on the epicardial surface of the heart ata location superior of an anterior annulus of the mitral valve.Preferably the frame 202 is non-flexible, having a permanentconfiguration which may not be readily bent to an ad hoc configurationthereby maintaining segments 162, 164 and 166 is fixed orientationsrelative to one another.

FIGS. 3A-3B are illustrations of a human heart 3, with the illustrationin FIG. 3B viewed with the pericardium 15 removed. The chambers of theheart 3 include the left ventricle 4, the left atrium 5, the rightventricle 6, and the right atrium 7. Also shown are the pulmonary trunk8, the aorta 9, the superior vena cava 19, the right pulmonary veins 11,the left pulmonary veins 12, and the left atrial appendage 13. Thetransverse sinus 14 is also referenced in FIG. 3A. The transverse sinus14 is a pericardial cavity between the pericardium 15 and the epicardialsurface of the heart 3 located posterior to the aorta 9 and thepulmonary trunk 8 and anterior to the left atrium 5 and the superiorvena cava 19. The pericardial sac or pericardium 15, which is a tissuemembrane covering the epicardial surface of the heart 3, is also shownremoved from the heart 3 in FIG. 3B to further illustrate noteworthyanatomy of the heart 3. The oblique sinus 16 is a blind (e.g.,cul-de-sac) recess on the posterior of the heart 3 formed between thepericardium 15 and the epicardial surface of the heart 3. The obliquesinus 16 lies generally between the right pulmonary veins 11 and theleft pulmonary veins 12, with the thoracic part of the inferior venacava 17 located on the side of the pulmonary veins 11. Only two layersof serous pericardium separate the transverse sinus 14 and the obliquesinus 16.

The devices described herein may be positioned on the epicardial surfaceof the heart 3 during a medical procedure. For example, in someembodiments the device 10 may be installed on the heart 3 during abeating heart surgery, without the need of a heart/lung bypass machine.For instance, the device 10 may be implanted on the heart 3 through anopen chest procedure (sternotomy) or a lateral thoracotomy. In someembodiments, the device 10 may be positioned on the heart 3 through aless-invasive endoscopic approach. For example, during a sternotomy, thethoracic cavity may be accessed for direct visual placement of thedevice 10 on the beating heart 3. For any of these procedures, thepericardium 15 may be incised to access the pericardial cavity betweenthe pericardium 15 and the epicardial surface of the heart 3. Uponaccessing the pericardial cavity, the device 10 may be properlypositioned on the epicardial surface of the heart 3.

For example, FIG. 4A is an anterior view of the heart 3, with the device10 placed on the epicardial surface of the heart 3. As shown in FIG. 4A,the anterior segment 162 of the device 10 is positioned in thetransverse sinus 14 posterior to the aorta 9 and the pulmonary trunk 8and anterior to the left atrium 5 and the superior vena cava 19. Thelateral segment 166 may extend around the left lateral side of the heart3 at a location inferior to the left atrial appendage 13. In otherembodiments, the lateral segment 166 may extend around the left lateralside of the heart 3 at a location superior to the left atrial appendage13 or over the left atrium 5.

FIG. 4B is a posterior view of the heart 3 with the device 10 placed onthe epicardial surface of the heart 3. As shown in FIG. 4B, theposterior segment 164 of device 10 is positioned on the posterior of theheart 3 inferior of the atrioventricular groove 18. The posteriorsegment 164 may be positioned such that it is just below the circumflexartery 21. In other embodiments, the posterior segment 164 may bepositioned such that it is just above the circumflex artery 21. Flap 85extends inferiorly of the posterior segment 164 and is attached tofoundation 185. Foundation 185 is anchored to the epicardial surface ofthe heart 3 in a position inferior of the posterior segment 164, at atarget location that establishes an anchoring base to fix the flap 85 tosecure the posterior segment 164 at the desired location, such as thatshown in FIG. 4B.

Thus, the anterior segment 162 may be located in the transverse sinus14. The posterior segment 164 may be positioned on the posterior side ofthe heart 3, such as on or inferior to the atrioventricular groove 18 orin the oblique sinus 16 and anchored in that position by fixing flap 85to foundation 185. The position of the posterior segment 164 can beadjusted, if needed, by detaching the flap 85 from the foundation 185,repositioning the posterior segment 164 to a new location, andreattaching the flap 85 to the foundation 185, all without the need toremove any tacks, screws or other fixators from the heart. In someembodiments, the posterior segment 164 may be positioned inferior to theatrioventricular groove 18 on the posterior side of the heart 3. Thelateral segment 166 may extend around the left lateral side of the heart3 such that the anterior segment 162 is properly positioned in thetransverse sinus 14 while the posterior segment 164 is properlypositioned on the posterior side of the heart 3, such as on or inferiorto the atrioventricular groove 18 or in the oblique sinus 16. In someembodiments, the lateral segment 166 may extend around the heart 3 at alocation inferior to the left atrial appendage 13. However, in otherembodiments the lateral segment 166 may extend around the heart 3 at alocation superior to the left atrial appendage 13 or over the leftatrium 5 to join the anterior segment 162 and the posterior segment 164.The anterior and posterior ends are spaced apart from one another by apredetermined distance and remain separated by a gap or opening aftercompletion of implantation of the device 10.

The devices 10 of the present invention, when properly positioned, mayreside on the epicardial surface of the heart 3, interior of thepericardium 15. Thus, positioning of the device 10 may not requirepenetration of the heart into one or more of the chambers of the heartand/or may not require the device 10 to come into contact with bloodbeing located inside the chambers of the heart 3. By placing the device10 on the epicardial surface, exterior of the interior of the heart 3,complications associated with surgical procedures in which access isrequired to one or more of the chambers of the heart 3 are avoided. Byanchoring foundation 185 to the surface of the heart and anchoring thedevice 10 to the foundation 185 (via flap 85), the device 10 can berepositioned, removed or replaced without the need to remove anyfixators from the surface of the heart 3, thereby making such procedureseasier, faster and safer, as no bleeding from the heart wall will resultfrom detachment of flap 85 from foundation 185 or from reattachment of abase 85 to foundation 185. Furthermore, the time required to completethe surgical procedure may be greatly reduced from the time required foran open heart surgery or a surgical procedure requiring accessing theheart 3 through the vasculature.

FIG. 5 is a top view of the ventricular portion of the heart 3 with theatria removed. With the atria removed, the mitral valve 22 between theleft atrium 5 (not shown in FIG. 5) and the left ventricle 4 is clearlyshown. Also shown is the tricuspid valve 23 between the right atrium(not shown in FIG. 5) and the right ventricle 6, as well as the aorticvalve 24 leading to the aorta 9 and the pulmonary valve 25 leading tothe pulmonary trunk 8. As shown in FIG. 5, the mitral valve 22 includestwo leaflets, an anterior leaflet 26 and a posterior leaflet 27. Themitral valve 22 is shown closed as it would be during systole. Thedevice 10 is shown in phantom (dashed lines) in FIG. 5 as the device 10may not lie in the plane of the mitral valve 22 shown.

When device 10 is properly placed around the heart 3 as illustrated inFIG. 5, the shape of the device 10 may reduce the anterior-posteriormeasurement of the mitral valve 22. In other words, the device 10 mayurge the posterior leaflet 27 of the mitral valve 22 and anteriorleaflet 26 toward one another, providing better contact (coaptation) ofthe anterior 26 and posterior 27 valve leaflets of the mitral valve 22,which may reduce or eliminate mitral regurgitation. Device 10 ismanually adjustable in ways already described above to reposition thedevice 10 and particularly the posterior segment 164 (with possibly alsosome alteration in the position of segment 166) by detaching flap 85from foundation 185, repositioning the device 10 to a desired position,and reattaching the flap 85 to the foundation 185. Thus, the placementof device 10 as shown in FIG. 5 can be installed in a manner to reduceor eliminate mitral valve regurgitation.

A method of treating mitral valve regurgitation as one preferred exampleof various methods of treatment that may be used to treat mitral valveregurgitation is now provided. In addition to variations of this methoddescribed, as well as variations in the particular device 10 used, it isfurther noted that the present devices are not limited to the treatmentof mitral valve regurgitation, as they could be used to treat tricuspidvalve regurgitation or regurgitation in another heart valve other thanthe mitral and tricuspid valves, and further could alternatively be usedto treat any of the tissues/organs identified herein.

An exemplary, non-limiting embodiment of a procedure for installing thedevice/clip 10 of FIG. 1A is now described. In this embodiment, theheart 3 is exposed by way of an open chest procedure, via a sternotomy,according to known techniques. Upon opening the chest, an anterior viewof the heart is directly visible to the surgeon. FIG. 6A illustrates ananterior view of the heart 3, with the left ventricle 4, left atrium andtransverse sinus labeled. The posterior surface of the heart 3 (FIG.6B), posterior surface of the ventricle 4, atrioventricular groove 18and the oblique sinus 16 therefore cannot be seen directly by the eyesof the surgeon.

Visualization of the blood flow through the mitral valve 22 can beprovided by echocardiography, for example to identify mitral valveregurgitation that may be occurring. The echocardiography providesimages that show blood flowing from the left atrium 5 through the mitralvalve 22 and into the left ventricle 4 (atrial systole) and alsoprovides images that can identify when blood flows retrograde from theventricle 4 through the mitral valve 22 and into the left atrium 5, amalady that typically occurs during ventricular systole. Ultrasoundenergy is applied to the heart 3 in the area of the left ventricle 4,mitral valve 22 and left atrium 5 to provide images that are transverseto the plane of the mitral valve annulus, which may or may not be normalto the plane, but are typically near to normal. However, other angles ofvisualization may also be used. FIG. 7A shows an echocardiogramillustrating occurrence of severe mitral valve regurgitation, where alarge, brightly colored plume 402 indicates the retrograde blood flowthrough the mitral valve, thus indicating the large volume ofregurgitation of blood from the ventricle that is occurring duringventricular systole. FIG. 7B shows an echocardiogram illustratingoccurrence of moderate mitral valve regurgitation where plume 404 issomewhat smaller than plume 402 and less brightly colored overall,indicating that the amount of retrograde blood flow through the mitralvalve 22 during ventricular systole is less than that shown in FIG. 7A.FIG. 7C shows an echocardiogram illustrating occurrence of mild mitralvalve regurgitation 402 during ventricular systole, wherein plume 406 isclearly much smaller than 402 and much smaller than 404. FIG. 7D showsan echocardiogram where no mitral valve regurgitation occurs duringventricular systole, as it can be seen that the left atrium is dark inthis echocardiogram. By providing real time echocardiography asdescribed, the surgeon/surgical team can visually ascertain the amountof mitral valve regurgitation as the heart 3 is manipulated in an effortto find a condition where reduction, minimization or elimination ofmitral valve regurgitation can be achieved.

To perform such manipulation, force is applied posteriorly to the heart3 on or inferior to the atrioventricular groove 18 or in the obliquesinus 16, in a location where the posterior segment 164 is intended tocontact the heart 3 upon implantation of the device/clip 10. FIG. 6Bindicates the general location 410 where the force is applied. Note thatbecause FIG. 6B is a posterior view of the heart 3, the surgeon cannotsee where the force is being applied, but it needs to be applied throughfeel to locate the appropriate location to apply the force. The amountof force and/or location of application of force applied may be variedwhile viewing the echocardiographs provided in real time on a monitoruntil a location and amount of force are applied that achieve a resultof reduction, minimization or elimination of mitral valve regurgitation.

When the location and amount of force applied for achieving a result ofreduction, minimization or elimination of mitral valve regurgitation areestablished, an echocardiogram taken in a plane (or approximating aplane) of the mitral valve annulus is provided, a schematic illustrationof which is shown in FIG. 8. A measurement of distance 460 between theepicardial surface of the posterior heart 3 wall and the epicardialsurface of the anterior heart wall in the transverse sinus 14, atlocations corresponding to locations of distance 160 measured in FIG.1A, on the heart 3 where those locations of the device/clip 10 areintended to be located, provides a measurement 460 that can be used toselect a device clip 10, wherein measurement 160 of device clip 10 isequal to measurement 460 (or nearest to measurement 460, as selectedfrom a kit of device clips 10 having different measurement distances160.

FIG. 9 is a view of a width sizing instrument 500 with a view of thecontact surface 556 c according to an embodiment of the presentinvention. The width 556W and length 556L are preferably the same ornearly the same as the width 56W and length 56L of the contact surface56 of device/clip 10 that is intended to be implanted, in order toprovide a close simulation of the manner in which force will be appliedthrough the contact surface 56 to the heart 3. Likewise, it is preferredthat the curvature and conformation of the contact surface 556 c be thesame, or closely matching that of the curvature of contact surface 56 c.At least the contact component 556 may be made from the same material asthe pad 56. However, because silicone is not highly visible underechocardiography, it may be preferable to include one or more contrastagents such as air bubbles encapsulated in the contact componentmaterial, low solubility fluorocarbon gas, polymer shell and lowsolubility gas, or other contrast materials known in the art. Furtheroptionally, a rod/rib 202 having the same characteristics (makeup,dimension, shape, etc.) of rod/rib 202 of the device 10 may be includedas shown. Length 556L may be in a range from 25 mm to 70 mm, 30 mm to 60mm, 40 mm to 50 mm, or 42 mm to 48 mm, for example. In one particularembodiment, length 556L was 45 mm. Width 556W may be in a range from 5mm to 30 mm, 10 mm to 25 mm, 12 mm to 20 mm, or 13 mm to 17 mm, forexample. In one particular embodiment, width 556W was 15 mm. Additionalembodiments of width sizing instruments that can be used in place of thewidth sizing instrument 500 of FIG. 9 are disclosed in co-pendingInternational Application Serial No. (PCT serial no. not yet assigned,Attorney's Docket No. MITR-005WO), titled “Epicardial Valve RepairSystem”, filed concurrently herewith and incorporated herein, in itsentirety, by reference thereto.

FIG. 10 is a schematic illustration of application of force throughwidth sizing instrument 500 to the posterior surface of the heart 3. Asnoted, this part of the procedure is performed with the heart 3 in thechest of the patient, in a position as close to its natural position aspossible to achieve the best measurement and positioning results. As theview illustrated in FIG. 10 is not visible to the surgeon, thisplacement is done by feel, using feedback provided by echocardiography.When the location and amount of force applied for achieving a result ofreduction, minimization or elimination of mitral valve regurgitation areestablished, the posterior surface of the heart 3 is marked to indicatewhere the placement of the sizing instrument 500 is currentlyestablished, as this will also establish the position where the sizinginstrument 500 is placed as the target location in which the posteriorsegment 164/pad 56 is to be placed. Marking may be performed using asurgical marker or some other type of biological ink applicator, orother biological marker, including, but not limited to those describedin Provisional Application Ser. No. 62/622,830, which is incorporatedherein, in its entirety. For example, width sizing instrument 500 may beconfigured to perform the marking. As shown the mark is made inferiorlyadjacent to the inferior edge of the sizing instrument 500. Additionallyor alternatively, marking may be performed at any other location definedby an established distance and orientation to a reference location ofthe posterior segment 164 that is to be placed.

Once the target position that the posterior segment is to occupy on theheart 3 has been established as described, the sizing instrument 500 isremoved and the heart 3 is lifted at least partially out of the chestcavity so that the surgeon can directly view the target position andmarking 502. Foundation 185 is next anchored to the epicardial wall ofthe posterior side of the heart 3, using fixators 504, such as tacks,screws, or equivalent, as illustrated in FIG. 11. The positioning of thefoundation 185 is relative to the marking 502, typically alignedtherewith, where the superior edge of the foundation 185 can be placedimmediately adjacent to or parallel to but spaced by a predetermineddistance from the marking 502. Other variations of the relationship ofthe positioning of the foundation 185 relative to the marking 502 mayexist, such as when the marking 502 is placed at a location other thanalong the inferior edge of the sizing instrument 500.

Device 10 can next be fixed to the epicardium of the heart 3. Theanterior segment 162 is inserted into the transverse sinus, and thelateral segment 166 wraps around so that the posterior segment can bepositioned in alignment with the marking 502. In the embodiment shown inFIG. 12, the inferior edge of the pad 56 of posterior segment 164 isaligned with the marking 502. To maintain this position, flap 85 isattached to foundation 185 as shown. Optionally the anterior segment maybe placed in a sleeve in the transverse sinus and the sleeve can beanchored to the transverse sinus with tacks, screws or other fixators.After fixing the device 10 to the heart 3 as described, the heart 3 canthen be lowered back into its natural position in the chest cavity.Additional echocardiography can be performed in the manner describedabove with regard to FIGS. 7A-7D to determine the amount of reduction ofMR regurgitation that has been accomplished. At this time it is possibleto adjust the device 10, and particularly the posterior segment 164, ifneeded to improve the results. This adjustment can be accomplishedeither in the chest cavity, or the heart can again be lifted and rotatedto perform the adjustment under direct visualization. Adjustment in thechest cavity is preferred, as it requires less time and manipulation,and can be readily performed by feel, as the surgeon can detach the flap85 from the foundation, reposition the posterior segment 164, andreattach the flap 85 to the foundation without the need to directlyvisualize any of these steps. The adjustment steps can be iterated asmany times as needed to optimize the reduction, minimization orelimination of mitral valve regurgitation. When the device 10 positionhas been optimized, the patient can be closed according to standardprocedures and the flap 85 remains fixed to the foundation 185 tomaintain the device 10 in the optimized position and orientation.Advantageously, the present invention allows a subsequent procedure tobe carried out in the future, should it become necessary to adjust theposition of the device 10 or remove the device 10 for any reason,including, but not limited to replacing it with a different sized device10. Any such additional procedure can be carried out without the need toremove the foundation 185 and therefore bleeding of the heart wall fromremoving fixators can be avoided.

FIG. 13 illustrates a number of events that can be carried out in amethod of implanting a device according to an embodiment of the presentinvention. After establishing an opening in the patient to provideaccess to the heart (which can be open-chest, a lateral thoracotomy, orendoscopic, as noted above, or other opening allowing access), anepicardial force is applied on a location of the heart, whilevisualizing regurgitation through the valve via visualization apparatusat event 1302. As noted above the force is typically applied to aposterior location of the heart adjacent the valve to be treated. Thelocation of the application of force and/or the amount of force appliedcan be varied, while continuing the visualization, at event 1304, untila combination of a location and amount of applied force is found wherevisualization confirms that valve regurgitation is reduced, minimized oreliminated to the satisfaction of the surgeon. The location of theapplication of force where it is found that the valve regurgitation isreduced, minimized or eliminated as described is considered to be thetarget location for application of force by a device to beimplanted/installed, and the target position is marked at event 1306according to any of the marking methods previously described.

At event 1308, a foundation is anchored to the epicardial surface of theheart to provide a base for fixing an epicardial device thereto. Thefoundation is fixed according to a predetermined relationship to themarked location so that attachment of the flap to the foundation willresult in the posterior segment of the device being located at thetarget location. At event 1310, the device 10 is fixed by attaching flap85 to the foundation 185. This establishes a segment of the device inthe target position and indirectly fixes the epicardial device to theheart 3 via the foundation 185.

To confirm that the device 10 has been properly placed for performanceas desired, further visualization of the functioning of the valve may becarried out after the attachment event of 1310. If it is seen that agreater amount of regurgitation is recurring than what was occurringduring visualization at the time that the target location wasidentified, then the surgeon may choose to detach the flap 85 from thefoundation, reposition the epicardial device 10 to reduce the amount ofregurgitation and verify reduction in regurgitation by furthervisualizing. The flap 85 is reattached to the foundation 185 and furtherverification can be performed using the visualization.

Any of the methods described herein may optionally further includemeasuring the distance between the target location when the force isapplied and the epicardial surface of the heart wall opposite the targetlocation, and using the measurement for selecting a device havingdistance 160 that best matches the measured distance, such as describedabove with regard to FIG. 8.

Further optionally, it may be desirable to perform a length measuringprocedure to establish an optimum length or length range for the length162L of the anterior segment 162 of the device/clip 10 that is to beused for the procedure. An optimal length 162L of the anterior segment162 is one which extends as far as possible into the transverse sinus14, without obstructing or potentially causing any damage to anystructures that may lie in the path of the transverse sinus 14. Thisprovides the greatest amount of securement of the clip/device 10 by theanterior segment portion 162 without unduly risking damage or trauma tothe surrounding tissues. Because the occurrence or existence of one ormore structures (such as a pulmonary vein or other vessel or structure)lying in the path of the transverse sinus 14 can vary from patient topatient, and because it is not possible to directly view suchoccurrences, it may be advantageous to perform a length measurement ofthe transverse sinus 14, to the extent that it is unobstructed, todetermine the maximum length of anterior segment 162 of a clip/device 10that can be safely used on a particular patient.

FIG. 14A is a perspective view, FIG. 14B is a plan view, and FIG. 14C isanother plan view (rotated ninety degrees about the longitudinal axis ofthe view of FIG. 14B) of a length sizing instrument 600 according to anembodiment of the present invention. Instrument 600 includes a shaft 602as the main body of the instrument. Shaft 602 is preferably a straightshaft and preferably has the same diameter as the diameter of the rod202 used in making the anterior segment 162 of device/clip 10. However,the diameter of 602 may be smaller, or even slightly larger than the rod202 and still function. Graduated markings 604 are provided along theshaft 602 to be referenced for making measurements of the unobstructedtransverse sinus 14. An atraumatic tip 606 may be formed at a distal endof the shaft 602 to prevent damage to tissues within the transversesinus 14 (such as obstructions, or the walls of the tissue forming thetransverse sinus) as the instrument 600 is being inserted into andadvanced along the transverse sinus 14. An enlargement 608 may be formedat the proximal end of the shaft 602 to function as a handle,facilitating the operation and manipulation of the instrument 600 by auser. In a preferred embodiment the instrument 600 is formed of the samematerials used to make a device/clip of the present invention. Forexample, shaft 602 in one specific embodiment has a titanium shaft, andthe atraumatic tip 606 and handle 608 are over-molds of silicone on theshaft 602. In another embodiment, atraumatic tip 606 and handle 608 areconfigured to form a friction fit with the shaft 602, such as by makingthe openings of the handle 608 and tip 606 of a smaller inside diameterthan is the outside diameter of the shaft 602. In one particularnon-limiting embodiment, these inside diameters were 0.381 mm less thanthe 3.175 mm outside diameter of shaft 602. Additional embodiments oflength sizing instruments that can be used in place of the length sizinginstrument 600 of FIGS. 14A-14C are disclosed in co-pendingInternational Application Serial No. (PCT serial no. not yet assigned,Attorney's Docket No. MITR-005WO), titled “Epicardial Valve RepairSystem”, filed concurrently herewith and incorporated herein, in itsentirety, by reference thereto.

FIG. 15 illustrates insertion of a length sizing device 600 into thetransverse sinus 14 of a heart 3 of a patient to be treated for mitralvalve regurgitation. The user typically grips the instrument 600 viahandle 608 and gently inserts the atraumatic tip 606 of the instrumentthrough the opening of the transverse sinus 14. While carefullyadvancing the tip 606/instrument 600 into the transverse sinus 14,pressure may be applied against the shaft 602 toward the heart wall soas to keep the shaft 602 as far against the wall and the interior wallof the transverse sinus 14 as practical, as this will be the most securelocation for the anterior segment 162. The instrument 162 is advanceduntil the end of the transverse sinus 14 is abutted by the atraumatictip 606 or until the atraumatic tip abuts a structure that extends intothe transverse sinus or until the atraumatic tip abuts an abrupt turn inthe transverse sinus 14 that occurs about when transverse sinusapproaches the right atrium. At this time, the graduated scale 600 isread by the user to measure the usable length of the transverse sinus.For example, if the graduated scale reads 55 mm at the opening of thetransverse sinus, then a device clip 10 having the longest anteriorsegment that is not greater than 55 mm would be selected for use in thiscase. Thus, if devices 10 having anterior segment 162 lengths of 45 mm,53 mm and 63 mm and 70 mm were available for selection, the devicehaving the anterior segment length 162L of 53 mm would be selected foruse in this case.

Once a preferred size (width 160 and length 162L) of device 10 has beenselected, the anterior segment 162 can be inserted into the transversesinus 14 and the posterior segment 164 can be positioned in the correctlocation on the posterior wall of the heart 3 identified during thewidth sizing procedure, and the posterior segment can be anchored to theposition by attaching flap 85 to foundation 185, as described above.Optionally, the anterior segment 162 may also be anchored in thetransverse sinus using tissue anchors, tacks or the like, insertedthrough a sleeve or a flap extending from the anterior segment 162.

FIG. 16A is a posterior, perspective view of an epicardially implantabledevice 10A according to another embodiment of the present invention. Inthis embodiment, device 10A may have any of the same characteristics ofdevice 10 described above with regard to FIG. 1A, in addition to thefeatures now described. In this embodiment, at least one additionalfoundation 285 is provided, in addition to the foundation 185. Althoughtwo additional foundations 285 are shown, alternatively only one or morethan two additional foundations may be provided, with an equal number ofextensions 385 to be attached thereto.

Extensions 385 extend inferiorly from the flap 85 or from pad 56 (FIG.17) or alternatively may extend from sheath 57 if employed, or, if thepad 56 is not included, the main frame 202 of the posterior segment 164.Extensions 385 may be made of any of the same materials descried formaking flap 85. Extensions 285 typically extend inferiorly from the flap85 by a distance in the range from 0.5 cm to 3 cm, preferably from about1 cm to 2 cm. Extensions 385, when attached to foundations 285, functionto apply compressive force between foundation 285 and foundation 185and/or posterior segment 164, which causes a reduction in tension on thechordae tendineae thereby facilitating better coaptation of the valveleaflets that the chordae tendineae are attached to, as described inmore detail below.

Foundation(s) 285, like foundation 185 is/are separately provided andis/are configured to be implanted to the surface of the heart, such asby anchoring using tacks, screws or other equivalent fixation means.Foundation 285 is a thin structure that can be fixed to the heart wallprior to anchoring the posterior segment 164. For example, foundation285 may be made from a thin layer of silicone or other structural corelayer to provide structure thereto, which may then be covered with anyof the same materials described above for use in making sheath 57.Alternative materials could be used that are biocompatible and flexible,but which have sufficient rigidity to provide structural support to thefoundation, such that it can be deformed to conform to the curvature ofthe surface of the heart that it is being anchored to, but retainssufficient rigidity so that it does not buckle, wrinkle, or otherwisedeform from its conforming shape. Optionally that core of the foundationmay not be covered. For example, once the target location for fixationof the posterior segment 164 is identified the one or more foundations285 can be fixed at positions that are located by a predetermineddistance inferior to the target location. For example, the predetermineddistance may be determined by a typical distance that the papillarymuscles and chordae tendineae extend from the valve leaflets (whenclosed) to the location on the internal wall of the heart where thechordae tendineae attach. The predetermined distance may be about thesame as this typical distance or slightly less, or slightly greater,preferably slightly greater. The predetermined distance may be in arange from about 2 cm to about 10 cm, typically from about 4 cm to about8 cm or from about 5 cm to 7 cm. Using the embodiments of FIG. 16A or17, the foundation 185 can be implanted on the heart wall in a locationthat will fix the posterior segment in the target location when flap 85is attached to foundation 185 and the foundations 285 can be implantedon the heart wall at predetermined distances from the target location ofthe posterior segment 164 so that, extensions 385 can be attachedthereto under tension, to apply compression force between anchors 285and posterior segment 164 and/or anchor 185.

To establish the attachment of extension 385 to foundation 285, thesurfaces of the extension 385 (see isolated view of anterior surface ofextension 385 in FIG. 16B) and foundation 285 that come into contactwith one another to accomplish the attachment are provided with matingattachment features 285A, 385A. The attachment features 285A, 385A maybe the same as any of those described above for attachment features 85A,185A. The surface area of the outer surface of foundation 285 may beequal to, less than or greater than the surface area of the surface ofextension 385 that it interfaces with. Preferably, the attachmentfeatures 385A may extend along a length portion 385L that is greaterthan the length 285L of foundation 285 to allow greater adjustability ofthe attachment of extension 385 to foundation 285 for varying the amountof tension applied.

FIG. 18 is a cutaway view of a human heart illustrating chordaetendineae 28 and papillary muscles 29 in the left 4 and right 6ventricles. The papillary muscles 29 in the left ventricle 4 attach tothe cusps of the mitral valve 22 and the papillary muscles 29 in theright ventricle 6 attach to the cusps of the tricuspid valve 30 via thechordae tendineae 28. FIG. 19 is an isolated view showing attachment ofthe papillary muscles 29 to the anterior leaflet 26 and posteriorleaflet 27 of the mitral valve 22 via chordae tendineae 28. Thepapillary muscles 29 contract to prevent inversion or prolapse of themitral valve leaflets 26, 27 (likewise, to prevent inversion or prolapseof the tricuspid valve leaflets by 29, 28 in the right ventricle) duringsystole (or ventricular contraction). The papillary muscles 29 of boththe right 6 and left 4 ventricles begin to contract shortly beforeventricular systole and maintain tension throughout. In the case of anormal heart 3 and heart valves, this prevents regurgitation, backwardflow of ventricular blood into the atrial cavities, by bracing theatrioventricular valves against prolapse (prolapse described by beingforced back into the atria by the high pressure in the ventricles).

However, in some cases of mitral and/or tricuspid regurgitation, thepapillary muscles 29 and/or chordae tendineae may apply too muchcontraction against the valve leaflets, either due to shortening of thechordae tendineae 28/papillary muscles 29 compared to normal, or otherreason. In these instances, reduction and or prevention of regurgitationmay be helped or accomplished reducing the amount of contraction orforce applied through the chordae tendineae 28. Attachment of extension385 to foundation 285 under tension can draw up the foundation 285somewhat toward the posterior segment 164, thereby somewhat shorteningthe distance therebetween, causing a relative reduction in tension onthe chordae tendineae 28, which, as a result will allow better closureof the mitral valve leaflets 26,27 during systole, thereby reducing oreliminating mitral valve regurgitation. In combination with thereshaping accomplished by forces applied to the mitral valve annulus 22A(e.g., see FIG. 8) by the anterior and posterior segments 162, 164, theforces applied to the ventricle 4 to reduce tension on the chordaetendineae 28 may cooperate to reduce or eliminate mitral regurgitation.It is further noted that the device 10′ could be adapted for similarfunctioning to reduce or eliminate tricuspid regurgitation from theright ventricle 6 through the tricuspid valve 30.

FIG. 20 is a partial, sectional view of a heart 3 on which device 10A isepicardially installed for treatment of mitral valve regurgitation,according to an embodiment of the present invention. The device 10A whenproperly positioned, applies forces to the valve annulus via at leastsegments 162, 164. As shown, flap 85 is attached to foundation 185 tomaintain the desired position and orientation of the posterior segment164, while anterior segment is maintained in the desired position in thetransverse sinus. Extension(s) 385 extends inferiorly from the flap 85and is attached to foundation 285 which has been anchored over orinferior of an epicardial location of the ventricle 4 that is appositeto one or more locations of insertion of chordae tendineae 28/papillarymuscle 29 into the inner wall of the ventricle 4. After installation ofthe device 10A as shown, manual adjustments can be made to change theposition/orientation of posterior segment 164 as described above.Additionally or alternatively, extension(s) 385 can be manually adjustedto change the amount of tension thereon by detaching extension 385 fromfoundation 285 and reattaching to shorten or lengthen the distancebetween the foundation 285 and the posterior segment 164 or flap 85.Adjustment of one or more extensions as described may therefore cause aconsequent reduction in tension on the chordae tendineae 28, which, as aresult may allow better closure of the mitral valve leaflets 26,27during systole, thereby reducing or eliminating mitral regurgitation.

FIG. 21 illustrates a number of events that can be carried out in amethod of implanting a device according to an embodiment of the presentinvention. After establishing an opening in the patient to provideaccess to the heart (which can be open-chest, a lateral thoracotomy, orendoscopic, as noted above, or other opening allowing access), anepicardial force is applied on a location of the heart, whilevisualizing regurgitation through the valve via visualization apparatusat event 2102. As noted above the force is typically applied to aposterior location of the heart adjacent the valve to be treated. Thelocation of the application of force and/or the amount of force appliedcan be varied, while continuing the visualization, at event 2104, untila combination of a location and amount of applied force is found wherevisualization confirms that valve regurgitation is reduced, minimized oreliminated to the satisfaction of the surgeon. The location of theapplication of force where it is found that the valve regurgitation isreduced, minimized or eliminated as described is considered to be thetarget location for application of force by a device to beimplanted/installed, and the target position is marked at event 2106according to any of the marking methods previously described.

At event 2108, foundation 185 is anchored to the epicardial surface ofthe heart to provide a base for fixing an epicardial device thereto. Thefoundation 185 is fixed according to a predetermined relationship to themarked location so that attachment of the flap 85 to the foundation 185will result in the posterior segment of the device being located at thetarget location. Additionally, one or more foundations 285 are anchoredto the epicardial surface of the heart 3 at a predetermined distanceinferior to the target location. This predetermined distance will havebeen predetermined to define location(s) that are generally apposite to(or slightly inferior or superior to a location apposite to) one or morelocations of insertion of chordae tendineae 28/papillary muscle 29 intothe inner wall of the ventricle 4. In a preferred embodiment employingan open chest procedure, the heart 3 is lifted so as to partially extendout of the chest cavity so that the surgeon can directly see thelocations on the posterior wall of the heart where the foundations 185and 285 are to be anchored, and the anchoring is performed with theheart 3 in this position.

At event 2110, the device 10A is installed by inserting the anteriorsegment 164 in the transverse sinus as described above and contactingthe posterior segment 164 to the posterior epicardial surface of theheart 3 at the target location. This location is fixed by attaching flap85 to the foundation 185. Additionally, extension(s) 385 is/are attachedto foundation(s) 285.

To confirm that the device 10 has been properly placed for performanceas desired, further visualization of the functioning of the valve may becarried out after the attachment event of 1310. In an open chestprocedure, the heart is returned to its original position where theposterior surface of the heart is no longer directly viewable by thesurgeon and visualization such as echocardiography is performed to checkthe degree of regurgitation, if any, that is occurring. If it is seenthat a greater amount of regurgitation is occurring than what wasoccurring during visualization at the time that the target location wasidentified, then the surgeon may choose to detach the flap 85 from thefoundation, reposition the epicardial device 10 to reduce the amount ofregurgitation and verify reduction in regurgitation by furthervisualizing. The flap 85 is reattached to the foundation 185 and furtherverification can be performed using the visualization. Additionally oralternatively, one or more extensions 385 may be detached fromrespective foundations 285 and reattached so as to increase or decreasethe amount of tension applied by the extension(s) 385. Visualization isagain performed to note any change in regurgitation resulting from suchadjustments. The events of FIG. 2112 can be repeated as many times asneeded until visualization confirms the adjustment levels of the flap 85and/or extension(s) 385 that provide satisfactory performance in thereduction or elimination of regurgitation.

Further optionally, it may be desirable to perform a length measuringprocedure to establish an optimum length or length range for the length162L of the anterior segment 162 of the device/clip 10 that is to beused for the procedure.

FIG. 22 illustrates events that may be carried out in the performance ofa minimally invasive procedure for epicardial implantation of a devicefor treatment of valve regurgitation according to an embodiment of thepresent invention. Although this embodiment is specifically directed toa procedure for treatment of mitral valve regurgitation, it can bereadily adapted to similar procedures for treatment of other valves,such as the tricuspid valve, aortic valve or pulmonary valve forexample.

At event 2202, ports are placed and trocars may be installed forfacilitating the procedures that follow. FIG. 23 illustrates locationsof port placement in a patient 1 according to one embodiment of thepresent invention. The port locations and number of ports are not to beconsidered limiting to the present invention, as the number andlocations of the ports may vary and may be a lesser or greater numberthan the number of ports shown in FIG. 23. In the embodiment shown inFIG. 23, a camera port 5202, which may be a size 8 port may be placed inthe 4^(th) intercostal space, midclavicular line for use in inserting acamera such as an endoscope therethrough and into the chest cavity ofthe patient 1. A superior tool port 5204, which may be a size 6 port,may be placed in the 2^(nd) intercostal space. An inferolateral toolport 5206, which may be a size 6 port, may be placed in the 6^(th)intercostal space, midaxillary line. An inferomedial tool port 5208,which may be a size 6 port, may be placed subxyphoid, and a deviceplacement port 5210, which is sufficiently large to allow device 10 ofFIG. 1A (or other device, such as a device for treatment of thetricuspid valve, for example) to pass therethrough, may be placed in the4^(th) intercostal space, midaxillary line. In a preferred embodiment,the device placement port 5210 may be an Alexis O WoundProtector/Retractor, available from Applied Medical. However, otherports having sufficient size and similar features may be substituted.Furthermore a smaller port 5210 may be used when the implantationprocedure uses a device having separate segments that can be assembledafter they have been passed through the port and into the chest cavity,like that disclosed in International Application Serial No. (serial no.not yet assigned, Attorney's Docket No. MITR-005WO), which has beenincorporated herein, in its entirety, by reference thereto above.

At event 2204 the chest cavity of the patient 1 is insufflated andsurgical tools and camera/endoscope may be placed through theappropriate ports. Insufflation may be to a pressure in a range of tento fifteen atmospheres, for example. The pericardium is accessed andopened sufficiently to allow placement of the device 10 (oralternatively, another device as described herein or in any of theapplications which have been incorporated by reference herein).Optionally, event 5106 may be carried out to assess the anteriorposterior dimension (usable length) of the transverse sinus 14, in orderto provide a length measurement for the anterior segment 162 of a deviceto be implanted, as described in detail above. A length sizinginstrument 600 can be inserted through one of the tool ports such as5204 using graspers and manipulated via the graspers to insert it intothe transverse sinus for measurement thereof. Using a robotic arm, thesizing tool 600 is grasped at its anterior dimension where it joins theend of the transverse sinus 14 and then the tool is withdrawn from thetransverse sinus. The camera can be used not only for the proceduresdescribed previously, but also to read the anterior-posterior dimension,or length where the robotic arm grasps the tool 600 as indicated bygradations 604. The sizing tool 600 can then be withdrawn from the chestcavity using the graspers.

Optionally, a width measurement may be performed at event 2208 to assessa width 160 to use for selecting a device that has a width 160 that mostclosely matches the measurement. To perform this assessment, a widthmeasuring instrument 500 may be placed through the device port 5210 andpositioned and manipulated using graspers or a handle 550 or 560 asdisclosed in International Application Serial No. (serial no. not yetassigned, Attorney's Docket No. MITR-005WO). Forces are applied by theinstrument 500, with repositioning as necessary, while visualizing themitral valve as described previously to determine when the instrument500 is positioned in the best location and with the best force appliedfor minimizing or eliminating mitral valve regurgitation. The widthmeasurement can be made at this time using the same visualizationtechniques described above. After the width measurement has beendetermined, the instrument 500 can be removed from the chest cavitythrough the device port 5210. It is noted that a similar procedure canbe carried out with regard to the tricuspid valve to measure a width ofa device to be used in treatment of the tricuspid valve.

At event 2210, a device is selected for implantation if it has notalready been selected (such as in instances where 2206 and 2208 are notperformed and the device is preselected, for example). In instanceswhere one or both of the optional events 5106, 5108 are carried out, thedevice can be selected to have an optimum anterior segment 162 lengthand/or distance 160D from various devices that are available forselection and which have varying anterior segment lengths and distances160D. At event 2212, the foundation 185 is introduced into the thoraciccavity by passing it through one of the ports (e.g., device port 5210)using graspers or other tool configured for operation from outside theport. Foundation 185 may be anchored to the epicardial surface of theheart to provide a base for fixing the epicardial device thereto. Thefoundation 185 is fixed according to a predetermined relationship to atarget location where the device is to be positioned to apply optimumforces to the epicardial surface of the heart. In instances where event2208 has been performed, the foundation is fixed at a location having apredetermined locational relationship to the marked location where thedevice is to apply force, so that attachment of the flap 85 to thefoundation 185 will result in the posterior segment of the device beinglocated at the target location. Optionally, one or more foundations 285may be introduce into the chest cavity at optional event 2214 throughone or more of the ports and may be anchored to the epicardial surfaceof the heart 3 at a predetermined distance inferior to the targetlocation. This predetermined distance will have been predetermined todefine location(s) that are generally apposite to (or slightly inferioror superior to a location apposite to) one or more locations ofinsertion of chordae tendineae 28/papillary muscle 29 into the innerwall of the ventricle 4 (or ventricle 6 if procedure is for tricuspidvalve). The foundation 185, as well as the foundations 285, whenoptionally used, may be anchored to the epicardial wall of the heart 3using tacks, helical screws, or other fixator, preferably of a type thatallows removal in instances where the foundation needs to be removed orreplaced. A fixator driver as described in International ApplicationSerial No. (serial no. not yet assigned, Attorney's Docket No.MITR-005WO) may be used to install the fixators through thefoundation(s) to anchor it to the epicardial wall.

At event 2216 the selected device may be introduced into the thoraciccavity through the device port 5210, using an implant insertion cradledescribed in International Application Serial No. (serial no. not yetassigned, Attorney's Docket No. MITR-005WO), graspers, forceps and orother instruments suitable for use in an endoscopic procedure. Thedevice port 5210 may be sealed with wetted gauze at the time ofplacement. If a width sizing procedure is performed (optional event2208) then the wetted gauze can be removed at that time. If event 2208is not performed, or if the wetted gauze was replaced after performingevent 2208, then the wetted gauze is removed at this time to open theport 5210 to allow the device to be delivered therethrough. The deviceis typically angled in orientation to allow it to be passed through theport 5210. For example the device may be angled to insert the anteriorsegment 162 first. After passing the device through the port 5210, thewetted gauze may be replaced over the port 5210 to help maintain theinsufflation pressure.

At event 2218 the device is manipulated via graspers, forceps and/orinsertion cradle to position the device in a desired relationship whereit partially surrounds the valve being treated and may be in, near orintersecting a plane of the valve, In a case where the valve beingtreated in the mitral valve, the anterior segment 162 of the device 10may be inserted into the transverse sinus 14. Visualization via thecamera can be used to ensure that force on the transverse sinus 14 isdirected toward the lateral wall. Optionally, transesophagealechocardiography (TEE) may be used to evaluate the left ventricledimensions and ensure that left atrial perforation does not occur. Atevent 2220 the device is attached to the foundation 185 and, optionally,one or more foundations 285, thereby anchoring the device in a desiredposition and orientation relative to the heart and the heart valve thatit is treating.

After completion of the implantation procedure or completion of removalof the device, all instruments/tools are removed, insufflation isceased, the ports are removed, and the patient is closed according tostandard procedures to complete the surgical procedure.

While the present invention has been described with reference to thespecific embodiments thereof, it should be understood by those skilledin the art that various changes may be made and equivalents may besubstituted without departing from the true spirit and scope of theinvention. In addition, many modifications may be made to adapt aparticular situation, material, composition of matter, process, processstep or steps, to the objective, spirit and scope of the presentinvention. All such modifications are intended to be within the scope ofthe claims appended hereto.

For example, any of the methods described herein can be practiced withother devices such as those described in any of the applications andprovisional applications that have incorporated by reference herein, intheir entireties. Thus, in addition or alternative to adjusting a deviceusing flap 85 and flap and/or flap 385, a device as described inApplication Ser. No. 62/622,831 may be used and manual adjustment of thedevice 10A, 10B or 10C in any of the manners described therein may beused to additionally or alternatively make adjustments to the forcesapplied by the device. Likewise in addition or alternative to adjustinga device using flap 85 and flap and/or flap 385, a device as describedin Application Ser. No. 62/622,827 may be used and automatic adjustmentof the device in any of the manners described therein may be used toadditionally or alternatively make adjustments to the forces applied bythe device.

1. An epicardial device for reducing or preventing regurgitation ofblood through a valve of a heart, said device comprising: a main bodyhaving a segment adapted to apply force to an epicardial surface of theheart; a member that applies counterforce to said force applied by saidsegment; a foundation configured to be anchored to the epicardialsurface of the heart, said foundation comprising a surface configuredwith attachment features; and said device further comprising a surfaceconfigured with mating attachment features configured to attach to saidattachment features of said foundation; wherein said mating attachmentfeatures and attachment features are separable and reattachable to allowrepositioning of at least a portion of said device relative to saidfoundation. 2.-22. (canceled)
 23. A method of epicardial treatment ofvalve regurgitation associated with a valve of a heart of a patient, themethod comprising: establishing at least one opening in the patient toprovide access to the heart; applying an epicardial force on a locationof the heart, while visualizing regurgitation through the valve viavisualization apparatus; varying at least one of the location or theamount of epicardial force applied to identify a target position wherevalve regurgitation is reduced or eliminated; marking the targetposition; anchoring a foundation to the epicardial surface of the heartto provide a base for fixing an epicardial device thereto; and fixingthe epicardial device to the foundation, wherein said fixing establishesa segment of said device in the target position and wherein said fixingindirectly fixes the epicardial device to the heart. 24.-28. (canceled)29. A method of epicardial treatment of mitral valve regurgitationassociated with a mitral valve of a heart of a patient, the anatomy ofthe heart including an aorta, a pulmonary trunk, a superior vena cava, atransverse sinus, a left atrial appendage, and an oblique sinus, themethod comprising: applying an epicardial force on a posterior locationof the heart, while visualizing regurgitation through the valve viavisualization apparatus; varying at least one of the location or theamount of epicardial force applied to identify a target position wheremitral valve regurgitation is reduced or eliminated; marking the targetposition; anchoring a foundation to the epicardial surface of the heartat a location having a predefined relationship to the marking; providinga clip having an anterior segment, an anterior end, a posterior segment,a posterior end and a lateral segment extending between the anteriorsegment and the posterior segment; positioning the anterior andposterior segments epicardially on the heart at locations apposite to anannulus of the mitral valve, such that the anterior and posteriorsegments apply force sufficient to reshape the annulus, wherein theposterior segment is located on the target position; fixing the clip tothe foundation, wherein said fixing maintains the posterior segment inthe target position. 30.-34. (canceled)